A Phase II Trial of Avelumab or Hydroxychloroquine With or Without Palbociclib to Eliminate Dormant Breast Cancer (PALAVY)

Plain English Summary

Avelumab or Hydroxychloroquine With or Without Palbociclib to Eliminate Dormant Breast Cancer is a Phase 2 clinical trial sponsored by Abramson Cancer Center at Penn Medicine studying Breast Cancer. This trial is testing if certain drugs (Avelumab, Hydroxychloroquine, Palbociclib) can eliminate tiny breast cancer cells that may remain after surgery and standard treatment. It is for women and men aged 18 and older who have had early-stage ER+/Her2- breast cancer, completed initial treatment, and have detectable dormant cancer cells in their bone marrow. Participants will receive one of four treatment combinations, either through injection or pills, for a period of time. They will have regular check-ups and tests. Alternative options include continuing standard endocrine therapy or participating in other clinical trials, depending on individual circumstances and physician recommendation. The trial aims to enroll 96 participants.

Official Summary

This clinical trial will assess the safety and early efficacy of Hydroxychloroquine or Avelumab, with or without Palbociclib, in early-stage ER+ breast cancer patients who are found to harbor disseminated tumor cells (DTCs) in the bone marrow after definitive surgery and standard adjuvant therapy.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are 18 or older, have been diagnosed with early-stage ER+/Her2- breast cancer, and have completed surgery, chemotherapy, and radiation. A key requirement is having detectable dormant cancer cells in your bone marrow after initial treatment, confirmed by a central lab. You cannot join if you have a history of other invasive breast cancers (unless diagnosed over 5 years ago), certain other prior cancers (unless disease-free for 5+ years), or have uncontrolled medical conditions like severe heart or lung issues. This trial is studying Breast Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary goal is to see if the study drugs can get rid of the small, dormant cancer cells found in the bone marrow, which could significantly reduce the risk of the cancer returning later. The specific primary outcome measures are: Determine the efficacy of HCQ or Avelumab, alone or in combination with Palbociclib, in eradicating DTCs (Efficacy is assessed at the end of Cycle 6 (each cycle is 28 days).). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical gap in treating early-stage breast cancer by targeting dormant cancer cells that can lead to recurrence, potentially offering a way to prevent the cancer from coming ba Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Breast Cancer, where improved treatment options are needed.

Investor Insight

This trial explores novel combinations for a large cancer market, with Palbociclib (a CDK4/6 inhibitor) already approved for advanced breast cancer, suggesting a potential pathway for regulatory appro Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific treatment you might receive, the potential side effects, and how this trial fits with your overall treatment plan. Participation involves regular visits for drug administration, blood tests, bone marrow tests, and imaging scans to monitor your health and the cancer's status. Be prepared for potential side effects and discuss any concerns with the study team promptly. This trial is currently recruiting participants. The trial is being conducted at 7 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 96 participants

Interventions

• DRUG: HCQ — 600 mg tablets twice daily D1-28 of each 28-day cycle
• DRUG: Avelumab — 10 mg/kg, IV, D1 and D15 of each 28-day cycle
• DRUG: Palbociclib — 125 mg capsule daily, by mouth on D1-21 concurrently with Avelumab. Or 75 mg capsule daily, by mouth on D1-28 concurrently with HCQ.

Primary Outcomes

• Determine the efficacy of HCQ or Avelumab, alone or in combination with Palbociclib, in eradicating DTCs (Efficacy is assessed at the end of Cycle 6 (each cycle is 28 days).)

Secondary Outcomes

• Determine the safety and tolerability of HCQ or Avelumab, alone or in combination with Palbociclib, in this Phase II study: adverse events (Toxicity is assessed from the first dose of study treatment through 30 days after the last dose of study treatment)
• Estimate the risk of recurrence after treatment with Palbociclib, Avelumab and HCQ, alone or in combination (Recurrence free survival (RFS) will be assessed 3 years after the completion of study treatment)

Full Eligibility Criteria

Inclusion Criteria:

* Bone marrow aspirate after completion of all definitive therapy demonstrates detectable DTCs (via IHC) as performed by central laboratory assessment at University of Pennsylvania.
* History of stage II-III histologically-confirmed ER+/Her2 neg invasive breast cancer with no evidence of recurrent local or distant disease (by American Joint Committee on Cancer 7th edition). Patients with bilateral breast cancer are eligible, so long as both cancers are ER+/Her2 neg, at least one meets other eligibility criteria and patient is treated with curative intent. For patients who undergo neoadjuvant therapy, eligibility is based upon pathologic stage of residual disease at surgery.
* ER+/Her2 neg receptor status on breast primary tumor (by American Society of Clinical Oncology/College of American Pathologists guidelines). Any partial response (PR) status is allowed. Tumors that are ER negative and PR positive are not eligible. Patients who undergo neoadjuvant therapy are eligible if either the pre-treatment biopsy or residual disease at surgery is ER+/Her2 neg.
* Patients must have completed all primary and adjuvant therapy (including surgery, chemotherapy, and radiation) with the exception of adjuvant endocrine therapy. Prior treatment-related toxicity must be resolved to ≤ Grade 1 with the exception of alopecia and peripheral neuropathy, prior to study enrollment.
* Patients may have received prior CDK4/6 inhibitor therapy with an agent other than Palbociclib. Patients must have discontinued CDK4/6 inhibitor at least 6 months prior to screening.
* Patients must be receiving adjuvant endocrine therapy at the time of enrollment. Patients are eligible to enroll within 2-7 years after initiation of adjuvant endocrine therapy. Use of tamoxifen as adjuvant endocrine therapy during study treatment is not allowed on hydroxychloroquine arms due to the potential drug-drug interaction with hydroxychloroquine. However, patients on tamoxifen at the time of screening may enroll on the treatment trial if switched to an aromatase inhibitor at least 21 days prior to starting study therapy in the event patient is randomized to a hydroxychloroquine containing arm. Premenopausal patients on concurrent ovarian suppression are eligible. Patients on any other adjuvant endocrine therapy, including any investigational therapy, are ineligible.
* Patients receiving bone modifying agents (bisphosphonates or rank-ligand inhibitors) at the time of screening may continue this therapy. Bone modifying agents may not be initiated while receiving study treatment.
* No concurrent enrollment on another investigational therapy clinical trial.
* Men and women, age ≥ 18 years.
* No contraindications to the study medications (refer to Section 7.2) or uncontrolled medical illness.
* Adequate bone marrow, liver, and renal function and other parameters.
* Ability to speak and understand English

Exclusion Criteria:

* Patients with a history of another prior invasive breast cancer are ineligible. Patients with prior Ductal carcinoma in situ (DCIS) of the breast are eligible if this was diagnosed \> 5 years prior to enrollment. Patients with prior invasive malignancy other than breast cancer are eligible if they have been disease-free for at least 5 years prior to enrollment.
* Patients receiving chronic, high dose systemic treatment with corticosteroids defined as: chronic use of cortisone \>50mg; hydrocortisone \>40mg, prednisone \>10mg, methylprednisone \>8mg or dexamethasone \>1.5mg; or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
* EKG demonstrating QT interval corrected (QTC) \> 480 ms
* Any severe and/or uncontrolled medical conditions or other conditions that could affect subject participation in the study including:

  * Chronic autoimmune disease
  * History or evidence of increased cardiovascular risk including any of the following:

    * Current clinical significant uncontrolled arrhythmias. Exception: Subjects with controlled atrial fibrillation
    * History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to enrollment
    * Current ≥ Class II congestive heart failure as defined by New York Heart Association
  * History of pneumonitis/interstitial lung disease or severely impaired lung function with a previously documented spirometry and Diffusing Capacity of Lung for Carbon Monoxide (DLCO) that is 50% of the normal predicted value (these tests not required at screening; prior results, if performed for standard of care should be referenced) and/or O2 saturation that is 88% or less at rest on room air
  * Uncontrolled diabetes
  * Active (acute or chronic) or uncontrolled severe infections
  * Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
  * HIV positive patient who are receiving combination anti-retroviral therapy are ineligible because of the potential

Trial Locations

• Georgetown University, Washington D.C., District of Columbia, United States
• University of Chicago, Chicago, Illinois, United States
• Indiana University, Indianapolis, Indiana, United States
• Dana-Farber Cancer Institute, Boston, Massachusetts, United States
• University of Pennsylvania, Philadelphia, Pennsylvania, United States
• Vanderbilt University, Nashville, Tennessee, United States
• University of Washington, Seattle, Washington, United States

Frequently Asked Questions

Related Conditions

• Breast Cancer
• ER-positive Breast Cancer
• HER2-negative Breast Cancer
• Dormant Cancer Cells
• Disseminated Tumor Cells
• Metastatic Breast Cancer
• Cancer Recurrence
• Adjuvant Therapy
• Endocrine Therapy
• Oncology

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